Back pain is one of the most common and often debilitating conditions affecting millions of people in all walks of life. It is estimated that over ten million people in the United States alone suffer from persistent back pain. Approximately half of those suffering from persistent back pain are afflicted with chronic disabling pain, sometimes referred to as chronic mechanical back pain, which seriously compromises the patient's quality of life and is the second most common cause of worker absenteeism. Furthermore, the cost of treating chronic back pain is very high, even though the majority of sufferers do not receive treatment due to health risks, limited treatment options and inadequate therapeutic results. Thus, chronic back pain has a significantly adverse effect on a person's quality of life, on industrial productivity, and on health care expenditures.
Chronic mechanical back pain has taken on many connotations by those skilled in the art. Chronic back pain has been defined as back pain that lasts for longer than 12 weeks. Others define chronic back pain as pain that lasts beyond the expected period of healing, and recognize that chronic pain may not have well-defined underlying pathological causes. Still others classify frequently recurring back pain as chronic pain since it intermittently affects an individual over a long period of time.
Approximately 97% of adult patients with low back pain have mechanical pain of non-cancer origin. In the majority of these patients, except for the presence of spondylotic disease, a precise pathoanatomical diagnosis cannot be identified. While risk factors include twisting and heavy lifting, obesity, bodily vibration, and poor conditioning, low back pain is common in people without these risk factors.
Treatment interventions vary widely among clinicians, and the most common therapeutic approaches either lack scientific evidence or are reported to be ineffective. It has been reported that most patients with low back pain in primary care will have stopped consulting about symptoms within three months after their initial consultation, but a third or more will still be experiencing low back pain and related disability one year after consultation.
The most costly services for low back pain are diagnostic procedures, surgery, and physical therapy. The most commonly used medications for chronic back pain are the non-steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, and opioid agents. These medications are of little or no value in alleviating the relatively high pain levels associated with spinal mechanical pain. Wide variations in the care of chronic low back pain suggest that there is professional uncertainty about the optimal approach, and attempts to prevent its occurrence have been unsuccessful. Because chronic pain problems do not respond reliably to many of the strategies used for the treatment of acute pain, and because inappropriate care for chronic pain conditions often leads to clinical exacerbation and increased suffering and disability, relatively non-invasive treatments specific for the relief of refractory back pain are needed to fulfill an urgent public health need.
Oral bisphosphonates are used in the treatment of osteoporosis and Paget's disease. They are poorly absorbed and often cause upper gastrointestinal toxicity.
Pamidronate, a bisphosphonate, having the formula C3H9NO7P2Na2 5H2O, has been administered intravenously for malignant hypercalcemia, severe osteoporosis with compression fractures, Paget's disease, and in the management of pathological fractures and bone pain secondary to metastatic cancer. The principal pharmacologic action of pamidronate is inhibition of bone resorption. Although the mechanism of antiresorptive action is not completely understood, several factors are thought to contribute to this action. Pamidronate adsorbs to calcium phosphate (hydroxyapatite) crystals in bone and may directly block dissolution of this mineral component of bone. In vitro studies also suggest that inhibition of osteoclast activity contributes to inhibition of bone resorption. In animal studies, at doses recommended for the treatment of hypercalcemia, pamidronate inhibits bone resorption apparently without inhibiting bone formation and mineralization. Pamidronate inhibits the accelerated bone resorption that results from osteoclast hyperactivity induced by various tumors in animal studies.
The recommended dose of pamidronate in moderate hypercalcemia is 60 to 90 mg, with dosages of 90 mg needed to treat severe hypercalcemia. For Paget's, the recommended dose of pamidronate is 30 mg daily, administered as a 4 hour infusion on 3 consecutive days for a total dose of 90 mg. For the management of pathological fractures and bone pain from metastatic cancer, pamidronate needs to be administered every 2-3 weeks in order to provide sustained pain relief.
Recently, it has been suggested that bisphosphonate may have a pharmacological role in the modulation of nociceptive pain, even in conditions unrelated to accelerated osteolysis or bone disease, with a possible, more general clinical application to pain control.
In 1999, Goicoechea et al. reported that alendronate, a bisphosphonate, injected intraperitoneally in mice, was able to reduce visceral pain induced by the administration of acetic acid into the abdomen. However, the doses that induced analgesia were close to those that induce toxicity.
In 2001, Bonabello et al. compared the antinociceptive effect of morphine and acetylsalicylic acid to that of four bisphosphonates; i.e., clodronate, alendronate, pamidronate and etidronate. When the various analgesics were injected into the tails of mice, a dose-dependent antinociception was observed with pamidronate, clodronate and acetylsalicylic acid, whereas etidronate and alendronate produce an analgesic effect only at the highest dose tested.
Neither Goicoechea et al. nor Bonabello et al. studied any long term pain antinociceptive effects resulting from the administration of a bisphosphonate.